Suspensão ou manutenção dos bloqueadores do receptor de angiotensina e inibidores da enzima conversora da angiotensina e desfechos clínicos em pacientes admitidos no hospital com infecção por Coronavírus (SARS-CoV2) de acordo com a severidade e progressão da doença: análise do estudo randomizado BRACE CORONA
Data
2022-08-25
Autores
Macedo, Ariane Vieira Scarlatelli [UNIFESP]
Orientadores
Lopes, Renato Delascio [UNIFESP]
Tipo
Tese de doutorado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
Objetivos: avaliar o efeito da descontinuação versus a continuação dos inibidores
da enzima de conversão da angiotensina (IECA) e bloqueadores do receptor da
angiotensina II (BRAs) em desfechos clínicos em pacientes com doença coronavírus
2019 (COVID-19) de acordo com a gravidade da doença basal. Métodos: foram
randomizados 659 pacientes com diagnóstico confirmado de COVID-19 e foram
classificados em doença COVID-19 leve ou moderada na apresentação hospitalar
baseado em valores de saturação de oxigênio no sangue e grau de acometimento
pulmonar em tomografias de tórax. O desfecho primário foi a proporção média do
número de dias vivos e fora do hospital em 30 dias, de acordo com a gravidade da
doença. Resultados: foram randomizados 659 pacientes com diagnóstico
confirmado de COVID-19 e classificados como apresentando COVID-19 leve ou
moderada na apresentação hospitalar usando saturação de oxigênio e imagens
pulmonares. O desfecho primário foi a proporção média do número de dias vivos e
fora do hospital em 30 dias, de acordo com a gravidade da doença. Na
apresentação hospitalar, 376 pacientes (57,1%) apresentavam gravidade leve e 283
(42,9%) gravidade moderada da COVID-19. Pacientes moderados eram mais
propensos a serem obesos (índice de massa corporal > 30 kg/m2
) (59,3% vs.
46,9%), a terem diabetes (37,5% vs. 27,7%) e apresentavam maiores taxas de
sintomas clínicos relacionados a COVID-19, incluindo febre (72,9% vs. 66,9%), tosse
(74,2% vs. 67,3%) e dispneia (65,4% vs. 44,9%) que os pacientes com gravidade
leve. Pacientes moderados tiveram um valor médio de proteína C reativa mais alto
(mediana de 5,8 mg/dL [IIQ 2,5-10,0] do que pacientes leves (mediana de 3,2 mg/dL
[IIQ 1,1-6,4]. Em pacientes classificados como leves na apresentação, houve
progressão de gravidade clínica durante a hospitalização em 169 de 376 (44,9%) a
doença moderada e 20 de 376 (5,3%) a doença grave. Em pacientes classificados
como moderados na apresentação hospitalar 44 de 283 (15,5%) progrediu em
gravidade clínica para doença grave. A mortalidade em 30 dias foi de 30% (6/20) em
pacientes que progrediram de doença leve a grave e 25% (11/44) em pacientes que
progrediram de doença moderada a grave. Não houve óbitos em 30 dias entre os
pacientes que progrediram de doença leve a moderada durante a hospitalização. Em
pacientes com doença leve, não houve diferença significativa no número de dias
vivos e fora do hospital entre a suspensão de IECA/BRA (média de 23,5 dias [DP 6,3
x
dias]) e continuação (média 23,8 dias [SD 6,5 dias]), com uma proporção média de
0,98 (IC 95% 0,92-1,04). No entanto, em pacientes com doença moderada, houve
menos dias vivos e fora do hospital com a descontinuação de IECA/BRA (média de
19,6 dias [DP 9,5)] do que a continuação (média de 21,6 dias [DP, 7,6]), com uma
proporção média de 0,90 (95% CI 0,81-1,00; p-interação = 0,01). Conclusão: o
impacto da descontinuação versus a continuação dos IECA/BRAs em dias de vida e
fora do hospital por 30 dias diferiu de acordo com a gravidade da doença COVID-19
basal. Ao contrário dos pacientes com doença leve, os pacientes com doença
moderada que continuaram IECA/BRAs tiveram mais dias vivos e fora do hospital
por 30 dias do que aqueles que descontinuaram IECA/BRAs. Isso sugere que
IECA/BRAs devem ser continuados para pacientes com COVID-19 de gravidade
moderada.
Aims: to explore the effect of discontinuing versus continuing angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) on clinical outcomes in patients with coronavirus disease 2019 (COVID-19) according to baseline COVID-19 disease severity. Methods and Results: we randomized 659 patients with a confirmed diagnosis of COVID-19 and classified them as having mild or moderate COVID-19 disease severity at hospital presentation using blood oxygen saturation and lung imaging. The primary outcome was the mean ratio of number of days alive and out of the hospital at 30 days according to disease severity. At hospital presentation, 376 patients (57.1%) had mild and 283 (42.9%) had moderate COVID-19 disease severity. Moderate patients were more likely to be obese (body mass index > 30 kg/m2 ) (59.3% vs. 46.9%), to have diabetes (37.5% vs. 27.7%), and higher rates of COVID-19 related clinical symptoms including fever (72.9 % vs. 66.9 %), cough (74.2% vs. 67.3%), and dyspnea (65.4% vs. 44.9%) that mild patients. Moderate patients had a higher median value of C-reactive protein (median 5.8 mg/dL [IQR 2.5-10.0] than mild patients (median 3.2 mg/dL [IQR 1.1-6.4]. In patients classified as mild at presentation there was progression of clinical severity during hospitalization in 169 out of 376 (44,9%) to moderate disease and 20 out of 376 (5,3%) to severe disease. In patients classified as moderate at hospital presentation 44 out of 283(15.5%) progressed in clinical severity to severe disease. Mortality in 30 days was 30% (6/20) in patients who progressed from mild to severe disease and 25% (11/44) in patients who progressed from moderate to severe disease. There were no deaths in 30 days among patients who progressed from mild to moderate disease during hospitalization. In patients with mild disease, there was no significant difference in the number of days alive and out of the hospital between ACEI/ARB discontinuation (mean 23.5 days [SD 6.3 days]) and continuation (mean 23.8 days [SD 6.5 days]), with a mean ratio of 0.98 (95% CI 0.92-1.04). However, in patients with moderate disease, there were fewer days alive and out of the hospital with ACEI/ARB discontinuation (mean 19.6 days [SD 9.5)] than continuation (mean 21.6 days [SD, 7.6]), with a mean ratio of 0.90 (95% CI 0.81–1.00; p-interaction = 0.01). Conclusion: the impact of discontinuing versus continuing ACEIs/ARBs on days alive and out of hospital through 30 days differed according to baseline COVID-19 disease severity. Unlike patients with mild disease, patients with moderate disease who continued ACEIs/ARBs had more days alive and out of hospital through 30 days than those who discontinued ACEIs/ARBs. This suggests that ACEIs/ARBs should be continued for patients with moderate COVID-19 disease severity.
Aims: to explore the effect of discontinuing versus continuing angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) on clinical outcomes in patients with coronavirus disease 2019 (COVID-19) according to baseline COVID-19 disease severity. Methods and Results: we randomized 659 patients with a confirmed diagnosis of COVID-19 and classified them as having mild or moderate COVID-19 disease severity at hospital presentation using blood oxygen saturation and lung imaging. The primary outcome was the mean ratio of number of days alive and out of the hospital at 30 days according to disease severity. At hospital presentation, 376 patients (57.1%) had mild and 283 (42.9%) had moderate COVID-19 disease severity. Moderate patients were more likely to be obese (body mass index > 30 kg/m2 ) (59.3% vs. 46.9%), to have diabetes (37.5% vs. 27.7%), and higher rates of COVID-19 related clinical symptoms including fever (72.9 % vs. 66.9 %), cough (74.2% vs. 67.3%), and dyspnea (65.4% vs. 44.9%) that mild patients. Moderate patients had a higher median value of C-reactive protein (median 5.8 mg/dL [IQR 2.5-10.0] than mild patients (median 3.2 mg/dL [IQR 1.1-6.4]. In patients classified as mild at presentation there was progression of clinical severity during hospitalization in 169 out of 376 (44,9%) to moderate disease and 20 out of 376 (5,3%) to severe disease. In patients classified as moderate at hospital presentation 44 out of 283(15.5%) progressed in clinical severity to severe disease. Mortality in 30 days was 30% (6/20) in patients who progressed from mild to severe disease and 25% (11/44) in patients who progressed from moderate to severe disease. There were no deaths in 30 days among patients who progressed from mild to moderate disease during hospitalization. In patients with mild disease, there was no significant difference in the number of days alive and out of the hospital between ACEI/ARB discontinuation (mean 23.5 days [SD 6.3 days]) and continuation (mean 23.8 days [SD 6.5 days]), with a mean ratio of 0.98 (95% CI 0.92-1.04). However, in patients with moderate disease, there were fewer days alive and out of the hospital with ACEI/ARB discontinuation (mean 19.6 days [SD 9.5)] than continuation (mean 21.6 days [SD, 7.6]), with a mean ratio of 0.90 (95% CI 0.81–1.00; p-interaction = 0.01). Conclusion: the impact of discontinuing versus continuing ACEIs/ARBs on days alive and out of hospital through 30 days differed according to baseline COVID-19 disease severity. Unlike patients with mild disease, patients with moderate disease who continued ACEIs/ARBs had more days alive and out of hospital through 30 days than those who discontinued ACEIs/ARBs. This suggests that ACEIs/ARBs should be continued for patients with moderate COVID-19 disease severity.